1,4-Dihydroxyanthraquinone-copper(II) supported on superparamagnetic Fe3O4@SiO2: An efficient catalyst for N -arylation of nitrogen heterocycles and alkylamines with aryl halides and click synthesis of 1-aryl-1,2,3-triazole derivatives

Article abstract of DOI:10.1039/c6ra16646f

1,4-Dihydroxyanthraquinone-copper(ii) supported on a superparamagnetic Fe₃O₄@SiO₂ catalyst was employed for the N-arylation of nitrogen heterocycles and alkylamines with aryl halides to afford the corresponding coupled products in good to excellent yields without using external ligands or additives as promoters. Also, we have reported this recyclable catalytic system for efficient synthesis of 1-aryl-1,2,3-triazole derivatives in excellent yields. The desired triazoles were obtained from the reaction of the corresponding aryl boronic acid derivatives, alkyne, NaN₃, and 0.5 mol% catalyst in water/acetonitrile as the solvent at room temperature without the additional use of an external reducing agent. These methods show notable advantages such as the heterogeneous nature of the catalyst, low catalyst loading, easy preparation, excellent yields, short reaction times and simplicity of operation. Also, the catalyst can be separated from the reaction mixture by applying a permanent magnet externally and can be reused in six consecutive reaction cycles without significant loss of activity.

Full text of DOI:10.1039/c6ra16646f

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: S. Zahmatkesh, M.
Esmaeilpour and J. javidi, RSC Adv., 2016, DOI: 10.1039/C6RA16646F.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
1,4-dihydroxyanthraquinone-copper(II) supported on superparamagnetic
Fe3O4@SiO2: An efficient catalyst for N-Arylation of nitrogen heterocycles
and alkylamines with aryl halides and click synthesis of 1-aryl-1,2,3-
triazole derivatives
Saeed Zahmatkesh,*a Mohsen Esmaeilpour,*b Jaber Javidi,c,d
aDepartment of Science, Payame Noor University (PNU), 19395ꢀ4697, Tehran, Islamic
Republic of Iran
bChemistry Department, College of Science, Shiraz University, Shiraz, Iran
cDepartment of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
dStudents Research Committee, School of Pharmacy, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
*Corresponding author. Tel.: +98 7116137738, fax: +98 7112286008.
Eꢀmail address: zahmatkesh1355@yahoo.com (S. Zahmatkesh); m1250m551085@yahoo.
com (M. Esmaeilpour)
Abstract
1,4ꢀdihydroxyanthraquinoneꢀcopper(II) supported on superparamagnetic Fe3O4@SiO2
catalyst was employed for the Nꢀarylation of nitrogen heterocycles and alkylamines with aryl
halides to afford the corresponding coupled products in good to excellent yields without
using external ligands or additives as promoters. Also, we have reported this recyclable
catalytic system for efficiently synthesis of 1ꢀarylꢀ1,2,3ꢀtriazole derivatives in excellent
yields. The desired triazoles were obtained from the reaction of the corresponding aryl bronic
acid derivatives, alkyne, NaN3, and 0.5 mol% of the catalyst in water/acetonitrile as the
solvent at room temperature without the additional use of external reducing agent. These
methods shows notable advantages such as heterogeneous nature of the catalyst, low catalyst
loading, easy preparation, excellent yields, short reaction times and simplicity of operation.
Also, the catalyst can be separated from the reaction mixture by applying a permanent
magnet externally and can be reused for six consecutive reaction cycles without significant
loss of activity.
Keywords
Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst; NꢀArylation; Copper; 1,2,3ꢀTriazoles; Click chemistry;
Magnetic separation
1. Introduction
Currently the design of heterogeneous metal catalysts that preserve stability and high
metal dispersion during the catalytic reactions are of great importance.1ꢀ4 These
1

RSC Advances
Page 2 of 21
View Article Online
DOI: 10.1039/C6RA16646F
heterogenized catalysts can be easily separated from the reaction mixtures, but,
homogeneous catalysts show higher catalytic activities than their heterogeneous
counterparts because of their solubility in reaction media, which increases catalytic
site accessibility for the substrate.5ꢀ7 However, recycling homogeneous catalysts is
often tedious and also it is complicated and costly to recycle homogeneous catalysts,
especially when noble and toxic metal complexes are used.8,9 To solve these problems,
the particles are often immobilized on various inorganic and organic supports, such as
metal oxides, mesoporous silica, polymers, carbon materials, ionic liquids, and so
on.10ꢀ14
The use of magnetic materials as immobilized supports for heterogeneous catalysis
has attracted a great deal of attention because of the merits of magnetic separation.15ꢀ17
Among transition metal nanoparticle catalysts, Fe3O4 nanoparticles have recently
received a lot of attention as excellent supports because of their unique properties
including low toxicity, large surfaceꢀtoꢀvolume ratio, biocompatibility,
superparamagnetism and their potential applications in various fields.18,19 Fe3O4
magnetic nanoparticles have been used in wide range of disciplines, including
magnetic resonance imaging, magnetic data storage, targeted gene therapy, magnetic
fluids, drug delivery systems, biotechnology/biomedicine, hyperthermia treatment of
cancer cells, biosensors, environmental remediation, ion exchange separation,
detoxification of biological fluids and catalysis.20ꢀ28 Also, magnetic separation could
be regarded as an attractive alternative to centrifugation or alternative as it prevents
the loss of catalyst and enhances its reusability.29
However, pure MNPs such as Fe3O4 nanoparticles trend to aggregate due to their
nanoscale and poorly dispersed in aqueous medium due to their hydrophobic
surface.30 This problem can be solved by coating of MNPs with inorganic shells or
hydrophilic polymers. Among these, coating with a silica layer as the stabilizer, which
prevents direct contact between the nanoparticles has attracted great attention in recent
years. Furthermore, the abound hydroxyl groups on the surface of silica layer provide
the opportunity to conjugate various function molecules for many special
applications.31,32
The formation of carbonꢀnitrogen bonds via crossꢀcoupling reactions represents a
powerful means for the preparation of various compounds important in
pharmaceutical, biological and material interest.33,34 Copperꢀcatalyzed Ullmannꢀtype
reactions are traditional methods to assemble these compounds.35,36 Nucleophilic
aromatic substitution with aryl halides can be mediated by copper or palladium
catalysts.37 The high cost and toxicity of palladium catalysts restrict their use on the
industrial applications. Thus, researchers have turned their attention toward the use of
more efficient metals, less expensive, and less toxic to replace palladium. The lower
cost of copperꢀbased catalytic systems makes them particularly attractive for largeꢀ
scale industrial applications.38 During the past years, several reports describing
copperꢀcatalysed methods have appeared in the literature.39,40 However, these copperꢀ
mediated methods often suffer from limitations such as drastic reaction conditions,
lack of generality, moderate yields, high cost and requirement for stoichiometric or
greater amounts of copper catalyst. Therefore, the development of a new catalytic
system to overcome these shortcomings and fulfill the criteria of a mild, efficient
protocol for CꢀN bond formation is still desirable and is in demand.
2

Page 3 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
1,2,3ꢀtriazoles are an important class of nitrogen heterocyclic compounds which have
biological activities and also wide applications in medicinal chemistry, material
science and synthesis.41,42 The main method for the synthesis of 1,2,3ꢀtriazoles is the
Huisgen 1,3ꢀdipolar cycloaddition reaction of azides with alkynes. This cycloaddition
reaction has become the model for click reactions.43 However, the disadvantage of
Huisgen’s reaction was the production of a mixture of 1,4 and 1,5ꢀdisubstituted
products.43 Consequently, finding new protocols for stereoselective triazole synthesis
is of interest.
In 2002, Rostovtsev et al reported the efficient synthesis of 1,2,3ꢀtriazoles form the
CuIꢀcatalyzed azide/alkyne cycloadition (CuAAC). Their methodology is completely
stereoselective which delivered 1,4ꢀdisubstituted triazoles under mild reaction
conditions.44 Since then, the “Click Chemistry” reaction between azide and alkyne
(CuAAC) has gained much attention and many copper catalysts were reported for this
transformation specially the heterogeneous ones.45 Therefore, variety of supports such
as zeolites,46 activated charcoal,47 silica48 and amine functionalized polymers49 were
used to immobilize CuI onto their surface. The problem frequently encountered with
applying these catalysts is the oxidation tendency of Cu1 to CuII or disproportion to
Cu0 and CuII which reduces the catalytic activity.50 To overcome this matter, other
groups have applied CuII in the presence of reducing agents or ligands51 and the most
general one is the use of CuSO4/sodium ascorbate in aqueous media.52 In addition,
variety of immobilized CuII were reported for 1,2,3ꢀtriazoles synthesis.53 Recently,
hydroxyapatiteꢀsupported CuII54 or CuIIꢀhydrotalcite 55 were reported for formation of
1,2,3ꢀtriazoles in the absence of base or reducing agents. They have reported that
NaN3 can reduce CuII to CuI beyond being an azidonation reagent. Many of the
reported synthetic protocols for the synthesis of triazole derivatives suffer from one or
more disadvantages such as the harsh reaction conditions, long reaction times, low
yields, tedious workup of the reaction mixture and difficulty in separation and
recovery of the catalyst. Thus, the development of an alternate milder and cleaner
procedure, which surpasses those limitations, is very much relevant for the synthesis
of 1ꢀarylꢀ1,2,3ꢀtriazole derivatives
.
Therefore, in continuation of our studies and to promote the methods of new synthetic
using recyclable catalysts,56 we focused our attention on a simple and efficient method
for NꢀArylation of nitrogen heterocycles and alkylamines with aryl halides and click
synthesis of 1ꢀarylꢀ1,2,3ꢀtriazole derivatives in the presence of 1,4ꢀ
dihydroxyanthraquinoneꢀcopper(II) immobilized on superparamagnetic Fe3O4@SiO2
nanoparticles as illustrated in Scheme 1.
3

RSC Advances
Page 4 of 21
View Article Online
DOI: 10.1039/C6RA16646F
R
N(H)ꢀheterocycle
or
Ar
B(OH)2
NaN3
ArꢀX
R2NH
N
N
ArꢀNꢀheterocycle
Ar
N
or
ArꢀNR2
R
:Fe3O4@SiO2-DAQ-Cu(II)
Scheme 1. NꢀArylation of nitrogen heterocycles and alkylamines with aryl halides and click
synthesis of 1ꢀarylꢀ1,2,3ꢀtriazole derivativesis using the Fe3O4@SiO2ꢀDAQꢀCu(П)
nanoparticles.
2. Results and discussion
First of all, the preparation of magnetic nanocatalyst with coreꢀshell structure was
presented by using nano Fe3O4 as the core, TEOS as the silica source and PVA as the
surfactant. Then, Fe3O4@SiO2 was coated with 1,4ꢀdihydroxyanthraquinoneꢀ
copper(II) nanoparticles.57 The Fe3O4, Fe3O4@SiO2 and Fe3O4@SiO2ꢀDAQꢀCu(П)
nanocatalysts were characterized by various methods such as fourier transform
infrared spectroscopy (FTꢀIR), Xꢀray diffraction analysis (XRD), transmission
electron microscopy (TEM), field emission scanning electron microscopy (FEꢀSEM),
dynamic light scattering (DLS), thermogravimetric analysis (TGA), vibration sample
magnetometer (VSM), Xꢀray photoelectron spectroscopic (XPS), N2 adsorptionꢀ
desorption isotherm analysis and inductively coupled plasma analyzer (ICP).57
To optimize the conditions for the Nꢀarylation reaction, initially the reaction between
iodobenzene and imidazole as the model reaction was examined in the presence of
various amount of the catalysts and the results are presented in Table 1.
The results show clearly that catalyst is effective for this transformation and in the
absence of it; the reaction did not take place even after higher reaction time (Table 1,
entry 8). The use of a lower catalyst loading resulted in incomplete reaction (Table1,
entries 9ꢀ11). Increasing the amount of catalyst gave no substantial improvement in
the yield (Table1, entry 12).
Among all the solvents tested, including EtOH, MeOH, H2O, MeCN, DMF, DMSO
and toluene, DMF gave the highest yield (Table 1, entries 1ꢀ7). The screening of the
reaction time indicates that 4 h reaction time is the most suitable to afford the highest
yield of product 3a (Table 1, entry 5). We then decided to screen various bases. In
general, we obtained superior results with cesium carbonate (Cs2CO3). Replacement
4

Page 5 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
of cesium carbonate by potassium carbonate (K2CO3), tripotassium phosphate
(K3PO4), triethylamine (Et3N), sodium acetate (NaOAc) or sodium hydroxide resulted
in significantly decreased yields (Table 1, entries 5, 13ꢀ17).
Also, during our optimization studies, various temperatures were examined and it was
found that the temperature plays a significant role in terms of reaction rate and
isolated yield and the best results were obtained at 100 ◦C (Table 1, entries 5, 18ꢀ22).
Thus, the optimum conditions were found to be 1.0 mmol of iodobenzene, 1.2 mmol
of imidazole, 0.45 mol% of the Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst and 2 mmol of
Cs2CO3 in DMF (3 mL) at 100 oC.
Table 1. Optimization of the amount of catalyst, solvent, base and temperature on the Nꢀ
arylation reaction.a
Entry Catalyst amount
(mol%)
Solvent
Base
Temp (°C) Time
(h)
Yield
(%)
21
29
0
56
92
89
75
0
34
69
84
91
63
71
26
8
8
8
8
4
4
8
8
8
8
4
4
8
8
8
8
8
8
8
6
4
4
1
2
3
4
5
6
7
8
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
None
EtOH
MeOH
H2O
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K3PO4
Et3N
NaOAc
NaOH
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Reflux
Reflux
Reflux
Reflux
100 oC
100 oC
110 oC
100 oC
100 oC
100 oC
100 oC
100 oC
100 oC
100 oC
100 oC
100 oC
100 oC
r.t
MeCN
DMF
DMSO
Toluene
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
9
0.2 mol%
0.3 mol%
0.4 mol%
0.5 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
0.45 mol%
10
11
12
13
14
15
16
17
18
19
20
21
22
37
65
Trace
42
74
60 oC
80 oC
90 oC
82
90
110oC
aReaction conditions: iodobenzene (1 mmol), imidazole (1.2 mmol), base (2 mmol), Fe3O4@SiO2ꢀDAQꢀCu(П)
catalyst and solvent (3 mL).
To examine the scope for this coupling reaction, we have investigated the reactions
using a variety of aryl halides and a wide range of N(H)ꢀheterocycles and amines as
the substrates under the optimized reaction conditions and the results are outlined in
Table 2. We found that aryliodides and aryl bromides containing electron releasing
groups (3b, 3e) as well as electron withdrawing groups (3c, 3g) reacted with
imidazole to give corresponding Nꢀarylated imidazoles. Presence of electronꢀ
withdrawing group such as nitro groups on aryl halides (Table 2, 3c, 3f) increased the
yield of the coupling reaction whereas an electron releasing groups such as methyl and
methoxy groups on aryl halides (Table 2, 3b, 3e, 3i, 3m) at para position decreased
reaction yield for the Nꢀarylation reaction. To test further the scope of this catalyst,
reactions with indole, 2ꢀmethylꢀ1Hꢀindole, 1Hꢀbenzimidazole and 1Hꢀpyrrole are
5

RSC Advances
Page 6 of 21
View Article Online
DOI: 10.1039/C6RA16646F
conducted, which resulted in a very good yield (Table 2, 3h-3o). When diamines such
as piperazine were employed, the reaction was complete within 6h affording 81%
yield (Table 2, 3p). Moreover, aryliodides underwent NꢀArylation of aliphatic amines
such as piperazine, phenylpiperazine, dibutylamine and diethylamine under similar
conditions to afford the corresponding products in high yields (Table 2, 3p-3t).
Further we have screened the chloroꢀderivatives for the Nꢀarylation of imidazole
(Table 2, 3u-3w). NꢀArylation of imidazole with chlorobenzene gave no coupled
product under the above conditions. However, an increase of catalyst loading (0.6
mol%) with longer reaction time at 130 oC provided 43% yield of the coupled product
(Table 2, 3u). Among chloroꢀderivatives, pꢀnitrochlorobenzene with a strong electronꢀ
withdrawing group resulted in quantitative yield (Table 2, 3v), whereas 2ꢀ
chloropyridine resulted in lower yield (Table 2, 3w).
Table 2. NꢀArylation of N(H)ꢀheterocycles and amines with aryl halides using Fe3O4@SiO2ꢀDAQꢀCu(П)
nanocatalyst.a,e
X=I, 3c: 2.5 h, 97%
X=Br, 3g: 4 h, 94%
X=I, 3a: 4h, 92%
X=Br, 3e: 8h, 85%
X=Br, 3d: 8h, 91%
X=I, 3h: 4h, 96%
X=I, 3b: 6h, 90%
X=Br, 3f: 5 h, 93%
X=I, 3i: 4h, 91%
X=I, 3m: 6h, 90%
X=I, 3l: 4h, 96%
X=Br, 3j: 4h, 95%
X=I, 3n: 3.5h, 94%
X=I, 3k: 7h, 81%
X=I, 3o: 5 h, 96%
X=I, 3pb: 6h, 81%
6

Page 7 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
X=I, 3q: 6h, 86%
X=I, 3t: 8h, 81%
X=I, 3r: 4h, 90%
X=I, 3s: 7h, 85%
X=Cl, 3uc,d: 24 h, 43%
X=Cl, 3vc: 14 h, 91%
X=Cl, 3wc: 18 h, 57%
aReaction conditions: aryl halide (1 mmol), amine (1.2 mmol), Cs2CO3 (2 mmol), Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst (0.45 mol%), DMF
(3 mL), 100 ◦C.
bReaction conditions: aryl halide (2 mmol), amine (1.2 mmol), Cs2CO3 (3 mmol), Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst (0.8 mol%), DMF (5
mL), 100 ◦C.
cReaction temperature: 130 ◦C.
dReaction with 0.6 mol% of Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst.
eIsolated yield.
For optimization of the reaction parameters for efficiently synthesis of 1ꢀarylꢀ1,2,3ꢀ
triazole derivatives, the reaction of phenyl acetylene (1.1 mmol), phenylboronic acid
(1 mmol) and sodium azide (2 mmol) were investigated in the presence of
Fe3O4@SiO2ꢀDAQꢀCu(П) as a catalyst in various solvents and also in the presence of
various amounts of catalyst. The results are summarized in Table 3. The optimized
reaction conditions were: 1.1 mmol of phenyl acetylene, 1.0 mmol of phenylboronic
acids, 2.0 mmol of sodium azide, 0.5 mol% of Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst and
3 mL of H2O/ACN (Table 3, entry 11).
Table 3. Optimization of the amount of catalyst and solvent in a oneꢀpot synthesis
of the model reaction.a
Entry Catalyst (mol%)
Solvent
CH3CH2OH
CH3OH
iꢀPrOH
CH2Cl2
CH3CN
DMSO
DMF
THF
Time (h)
Yield (%)b
10
10
10
10
10
10
10
10
10
10
4
24
10
10
6
4
5
82
78
35
36
78
71
67
26
33
82
95
ꢀ
31
64
81
91
92
1
2
3
4
5
6
7
8
0.5 mol%
0.5 mol%
0.5 mol%
0.5 mol%
0.5 mol%
0.5 mol%
0.5 mol%
0.5 mol%
0.5 mol%
0.5 mol%
0.5 mol%
None
9
Toluene
H2O
10
11
12
13
14
15
16
17
H2O/ACN
H2O/ACN
H2O/ACN
H2O/ACN
H2O/ACN
H2O/ACN
H2O/ACN (1:1)
0.1 mol%
0.2 mol%
0.3 mol%
0.4 mol%
0.6 mol%
7

RSC Advances
Page 8 of 21
View Article Online
DOI: 10.1039/C6RA16646F
aReaction conditions: phenylboronic acid (1 mmol), sodium azide (2 mmol), phenyl acetylene (1.1
mmol), Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst and solvent (3 mL).
bIsolated yield.
After optimizing the reaction conditions, scope of the Fe3O4@SiO2ꢀDAQꢀCu(П)
catalyzed oneꢀpot CuAAC was investigated for variety of boronic acids and alkynes.
The results are summarized in Table 4. Various substituted aromatic and
heteroaromatic boronic acids and different aromatic and aliphatic alkynes were
investigated (Table 4). It was noticed that the triazole products were formed in
excellent yields with varying reaction times. The substrate scope of on pot synthesis
clearly shows that the reaction time depended on both aryl boronic acid as well as
alkyne (Table 4). However, reaction of phenyl boronic acid with phenyl acetylene
required 4h for completion of the reaction (Table 4, 7a). 4ꢀPhenoxyphenyl boronic
acids as well as formyl substituted phenyl boronic acid produced corresponding
triazoles in 5 h (Table 4, 7d,e). In contrast, as seen in Table 4, the present method is
not only suitable for aromatic alkynes but can also successfully be applied to aliphatic
alkynes (7g-l). Heteroaromatic boronic acids such as thiophenꢀ3ꢀylboronic acid and
indolꢀ5ꢀyl boronic acid participated well in these reactions producing corresponding
triazoles in excellent yields (Table 4, 7f,j).
Table 4. Fe3O4@SiO2ꢀDAQꢀCu(П) catalyzed oneꢀpot synthesis of 1ꢀarylꢀ1,2,3ꢀtriazoles.a
7b: 2.5h, 97%
7c: 3h, 97%
7a: 4h, 95%
7d: 5h, 87%
7e: 5h, 92%
7f: 3h, 95%
7i: 6h, 85%
7h: 3h, 95%
7g: 2h, 97%
8

Page 9 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
7j: 5h, 90%
7k: 1.5h, 94%
7l: 3h, 95%
aReaction conditions: Aryl boronicacid (1 mmol), sodium azide (2 mmol), alkyne (1.1 mmol), Fe3O4@SiO2ꢀDAQꢀCu(П)
catalyst (0.5 mol%), H2O/ACN (1:1), rt.
A mechanism for the catalytic activity of Fe3O4@SiO2ꢀDAQꢀCu(П) in the synthesis of
1ꢀarylꢀ1,2,3ꢀtriazole derivatives is shown in Scheme 2. The mechanism of CuAAC
revealed that sodium azide, which is used as azidonating reagent in oneꢀpot protocol
reduces Cu(II) to clickꢀactive Cu(I).58 Thus, the plausible mechanism for oneꢀpot
Fe3O4@SiO2ꢀDAQꢀCu(П) catalyzed CuAAC reaction is depicted in the Scheme 2.
Scheme 2. Plausible mechanism of oneꢀpot synthesis of 1ꢀarylꢀ1,2,3ꢀtriazoles using
Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst.
The recycling of the catalyst is an important issue in heterogeneous catalysis system.
Thus, we turn our attention to reusability of our Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst in
the preparation of 1ꢀphenylꢀ1Hꢀimidazole (3a) and 1,4ꢀdiphenylꢀ1Hꢀ1,2,3ꢀtriazole
(7a) under optimized conditions. It is noteworthy that the catalyst could be used six
times without significance loss of its activity (Fig 1a). Thus, it is reasonable to believe
that the immobilized catalyst can be repeatedly used for largeꢀscale production
without significant loss of its catalytic activity.
The superparamagnetic property of the particle is very important for its application.
9

RSC Advances
Page 10 of 21
View Article Online
DOI: 10.1039/C6RA16646F
As shown in Fig. 1b, the magnetic Fe3O4@SiO2ꢀDAQꢀCu(П) particles in solution
were black emulsion, and it could be separated from solution in a short period under
an external magnetic field. Thus, the attraction and dispersion processes can be readily
altered by applying and removing an external magnetic field, showing good dispersion
and magnetic separation.
Also, the morphology of the recycled Fe3O4@SiO2ꢀDAQꢀCu(П) particles after six
runs was analyzed. Figure 1c show representative TEM image of the catalyst after 6
cycles of catalytic reaction. As revealed by TEM, the obtained magnetite particles
possess approximately spherical shapes and a mean diameter of 60 nm (Fig. 1c).
Fig 1. (a) Recyclability of Fe3O4@SiO2ꢀDAQꢀCu(П) in the synthesis of 3a and 7a under the
optimized conditions; (b) Photograph of a magnet attracting Fe3O4@SiO2ꢀDAQꢀCu(П) in
solution; (c), (d) TEM and DLS images of Fe3O4@SiO2ꢀDAQꢀCu(П) nanoparticles after six
reaction cycles.
We did not observe significant change in the morphology of the catalyst, but some
particles might have aggregated. DLS measurements were also carried out to measure
the hydrodynamic diameter of the nanoparticles after six reaction cycles. This size
distribution is centered at a value of 70 nm (Fig. 1d). Generally, the size of
nanoparticles will be increased after each cycle and leaching of copper, and increasing
of catalyst size lead to a decrease in the yield.
10

Page 11 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
To determine the exact species responsible for the observed reactions and to measure
the extent of Cu leaching after the reactions, we have used the hot filtration test.59,60
For this aim, we have studied the reaction of iodobenzene, imidazole and cesium
carbonate in the presence of Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst under optimized
conditions. When the reaction was half complete, the nanoparticles were removed in
situ at the reaction temperature, and the reactants were allowed to undergo further
reaction in the solution. We confirmed that there was no further conversion of the
reactants in the absence of the nanoparticles. These results indicate that there was little
of the active metal species in the solution phase and confirmed that the catalyst acts
heterogeneously in the reaction.
Also, In order to determine the absolute amount of the copper species dissolved in
solution caused by leaching, the crude reaction mixtures were evaporated to dryness
and analyzed using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICPꢀ
AES). It was shown that 2.67 wt % (0.0061 mmol/g) of the total amount of the
original copper species was lost into solution during the course of the reaction after six
cycles. Therefore, the analysis of the reaction mixture by the ICP technique showed
that the leaching of Cu was negligible.
.
3. Conclusion
In conclusion, we developed a mild and practical Fe3O4@SiO2ꢀDAQꢀCu(П) catalyzed Nꢀ
arylation of N(H)ꢀheterocycles and alkylamines with aryl halides to afford corresponding
coupled products in good to excellent yields without using any external ligands or additives
as promoters. NꢀArylated products were isolated in good to excellent yields, demonstrating
the versatility of the protocol. This heterogeneous catalyst, also efficiently works for the
efficient triazole synthesis stating from NaN3, alkynes, and aryl bronic acid derivatives in
H2O/ACN at room temperature. Heterogeneous nature, thermal stability, easy separation of
the catalyst, simple procedure, excellent yields, short reaction time, easy product separation
and lower loading of catalyst makes this method an instrumental alternative to the previous
methodologies for the scale up of these reactions. In addition, these methods offer the
competitiveness of recyclability of the catalyst without significant loss of catalytic activity,
and the catalyst could be easily recovered by external magnetic field and reused for at least 6
cycles.
4. Experimental
4.1. Materials and physical measurements
All chemicals were of analytical grade and used as received. The progress of the
reactions was followed by TLC using silica gel SILG/UV 254 plates. IR spectra were
recorded with KBr pellets using a Shimadzu 8300 spectrophotometer. Xꢀray
diffraction (XRD) pattern was recorded on a Bruker AXS D8ꢀadvance Xꢀray
diffractometer using Cu Kα radiation (λ = 1.5418A°). The morphology and size of the
particles were examined by transmission electron microscopy (TEM) using a Philips
EM208 transmission electron microscope. Field emission scanning electron
microscopy (FEꢀSEM) was recorded on a Hitachi Sꢀ4160 instrument.
11

RSC Advances
Page 12 of 21
View Article Online
DOI: 10.1039/C6RA16646F
Particle sizes of MNPs were measured using a HORIBAꢀLB550 dynamic light
scattering. The Xꢀray photoelectron spectra (XPS) were recorded on the XR3E2 (VG
Microtech) twin anode Xꢀray source using AlKα= 1486.6 eV. The 1H and 13C NMR
spectra were recorded on a Bruker Avance DPX 250 MHz spectrometer (using CDCl3
with TMS as the standard). The Cu analysis and leaching test was carried out by ICP
analyzer (Varian, Vistaꢀpro). The element analyses (C, H, N) were obtained from a
Thermo finigan Flash EAꢀ1112 CHNSO rapid elemental analyzer. Melting points
were recorded with an Electrothermal Type 9100 melting point apparatus. Therefore,
all of the products were characterized by FTꢀIR, 1H NMR and 13C NMR, and also by
comparison with authentic samples.
4.2. General procedure
4.2.1. Preparation of Fe3O4@SiO2 core-shell
The preparation of Fe3O4 nanoparticles were performed according to the previous
reports.61 Briefly, FeCl3.6H2O (1.3 g, 4.8 mmol), 0.9 g of FeCl2.4H2O (4.5 mmol) and
polyvinyl alcohol (PVA 15000) (1 g) as a surfactant were dissolved in 30 mL of
water. The mixture was stirred vigorously for 30 min in 80 ◦C. Then, to this mixture,
hexamethylenetetramine (HMTA) (1.0 mol/L) was added with vigorous stirring. After
the color of bulk solution turned to black (pH: 10.0), the magnetite precipitates were
continuously stirred with N2 protection at 60 ◦C for 2 h. Subsequently the obtained
magnetite particles were separated from the suspension using a permanent magnet and
washed with ethanol three times and dried at 80 oC for 10 h.
Then, Fe3O4@SiO2 coreꢀshell nanospheres were prepared through a modified Stöber
method.62 In a typical process, .05 g of synthesized Fe3O4 nanoparticles were
dispersed in solution composed of 5 mL of deionized water, 50 mL of ethanol and 5
mL of NaOH (10 wt%). Subsequently, 0.2 mL TEOS (tetraethoxysilane) was slowly
added and the mixture was stirred vigorously. After being stirring for 30 min, the
Fe3O4@SiO2 nanoparticles were magnetically collected, washed with ethanol and
deionized water, and then dried under vacuum at 80 ◦C for 10 h.
4.2.2. General procedure for the preparation of functionalized Fe3O4@SiO2
nanoparticle with 3-(triethoxysilyl)-propylamine (Fe3O4@SiO2-NH2)
The obtained Fe3O4@SiO2 nanoparticles (1 g) were dispersed in 10 mL ethanol
solution by sonication for 20 min, and then 3ꢀaminopropyl (triethoxy) silane (1 mmol,
0.176 g) was added to the mixture. The above mixture was stirred vigorously and
refluxed for 12 h under nitrogen atmosphere. Then, the as prepared functionalized
MNPs nanoparticles were separated by an external magnet and washed thoroughly
with ethanol and water to remove the unattached substrates. Finally, the precipitated
product (Fe3O4@SiO2ꢀNH2) was dried in oven at 80 ◦C for 6 h.27
12

Page 13 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
4.2.3. Preparation of (4-hydroxy-9,10-dioxo-9,10-dihydroanthracen-1-yloxy)-
acetic acid ethyl ester (2)
In a typical run, a mixture of DMF (10 mL), ethyl 2ꢀbromoacetate (0.5 mmol), 1,4ꢀ
dihydroxyanthraquinone (1.0 mmol) and tꢀBuOK (0.5 mmol) was intensively stirred
at room temperature. The reaction was monitored by TLC and it was found to be
completed by 18 h. After completion of the reaction, 20 ml water was added, the
mixture was filtered, and the residue was dried. The crude product (2) was purified by
silica gel column and eluted with EtOAc:nhexane (1:1) to afford pure compound.60
4.2.4. Preparation of Fe3O4@SiO2-DAQ nanoparticles
The modification of Fe3O4@SiO2ꢀNH2 with 4ꢀhydroxyꢀ9,10ꢀdioxoꢀ9,10ꢀ
dihydroꢀanthracenꢀ1ꢀyloxy)ꢀacetic acid ethyl ester (2) was carried out via ligand
formation between the amino group and the carbonyl group of ester (2). In brief, the
asꢀprepared Fe3O4@SiO2ꢀNH2 (0.5 g) nanoparticles were suspended in ethanol (10
mL). After addition of 4ꢀHydroxyꢀ9,10ꢀdioxoꢀ9,10ꢀdihydroꢀanthracenꢀ1ꢀyloxy)ꢀacetic
acid ethyl ester (2) (1 mmol, 0.325 g), the mixture was refluxed stirring under inert
atmosphere for 24 h. Then, the resulting product (Fe3O4@SiO2ꢀDAQ) was collected
by a magnet, washed with distilled water and ethanol and dried under vacuum at 70
oC.60
4.2.5. Preparation of Fe3O4@SiO2-DAQ-Cu(II) nanoparticles
Fe3O4@SiO2ꢀDAQ (0.5 g) was dispersed into 10 mL of absolute ethanol, and 0.182 g
of Cu(OAc)2 (1 mmol) was added into this dispersion, then this mixed system was
refluxed for 24 h at the nitrogen atmosphere. The obtained Fe3O4@SiO2ꢀDAQꢀCu(II)
NPs were collected by magnetic separation and washed with deionized water and
ethanol three times and finally dried under vacuum at 80 oC for 10 h.60
4.2.6. General procedure for the N-Arylation of amines with aryl halides
In an oven dried 10 mL roundꢀbottom flask, aryl halide (1 mmol), amine (1.2 mmol),
Cs2CO3 (2 mmol), Fe3O4@SiO2ꢀDAQꢀCu(П) magnetic catalyst (0.02g, 0.45 mol%)
and DMF (3 mL) were stirred under nitrogen atmosphere at 100 ◦C and the reaction
was monitored by TLC. After completion of the reaction and separation of the
nanocatalyst with an external magnetic field, water (20 ml) was added and the mixture
was extracted with ethyl acetate. The organic phase was washed with water (2×5 ml)
and dried over anhydrous Na2SO4 and concentrated to get the crude product. The
resulting crude product was purified by flash chromatography to give the desired
products.
4.2.7. General procedure for one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
13

RSC Advances
Page 14 of 21
View Article Online
DOI: 10.1039/C6RA16646F
To a flask equipped with a magnetic stir bar, aryl boronic acid (1.0 mmol), sodium
azide (2.0 mmol), alkyne (1.1 mmol), Fe3O4@SiO2ꢀDAQꢀCu(П) catalyst (0.022g, 0.5
mol%), and H2O/ACN (1:1) (3.0 mL) were added and the mixture was stirred at room
temperature. The progress of the reaction was monitored by thin layer
chromatography (TLC). After stirring for the appropriate time, the catalyst was
removed using magnetic field. Then, the filtrate was extracted with EtOAc (3×10 mL)
and dried over anhydrous sodium sulfate. Combined organic layer was evaporated to
dryness, and the solid residue recrystallized from EtOH/H2O (1:3 v/v) to give a
crystalline pure product.
Spectral data
1-Phenyl-1H-imidazole (3a)
Dark brown oil, 1H NMR (250 MHz, CDCl3): δ= 7.14ꢀ7.45 (m, 7 H), 7.80 (s, 1 H); 13C NMR
(62.9 MHz, CDCl3): δ= 118.2, 121.4, 127.5, 129.9, 130.4, 135.5, 137.4.
2-Imidazol-1-ylpyridine (3g)
Dark brown oil, 1H NMR (250 MHz, CDCl3): δ= 7.14ꢀ720 (m, 2 H), 7.28ꢀ7.34 (m, 1 H),
7.25ꢀ7.34 (m, 1 H), 7.58 (s, 1 H), 7.73ꢀ7.80 (m, 1 H), 8.28 (s, 1 H), 8.41ꢀ8.43 (m, 1 H);13C
NMR (62.9 MHz, CDCl3): δ= 112.3, 116.7, 122.0, 130.6, 132.2, 134.9, 139.0, 149.1; Anal.
Calcd for C8H7N3: C, 66.19; H, 4.86; N, 28.95%. Found: C, 65.89; H, 4.97; N, 29.14%.
1-Phenyl-1H-indole (3h)
Dark brown oil, 1H NMR (250 MHz, CDCl3): δ= 6.59ꢀ6.63 (m, 1 H), 7.06–7.17 (m, 2 H),
7.25ꢀ7.30 (m, 2 H), 7.41ꢀ7.52 (m, 5 H), 7.59ꢀ7.64 (m, 1 H); 13C NMR (62.9 MHz, CDCl3): δ=
103.6, 110.5, 120.4, 121.1, 122.4, 124.4, 126.4, 128.0, 129.3, 129.6, 135.8, 139.8; Anal.
Calcd for C14H11N: C, 87.01; H, 5.75; N 7.25%. Found: C, 86.91; H, 5.86; N, 7.23%.
1-p-Tolyl-1H-indole (3i)
Dark brown oil, 1H NMR (250 MHz, CDCl3): δ= 2.35 (s, 3 H), 6.58 (dd, J= 4.2 Hz, 1 H),
7.04ꢀ7.32 (m, 7 H), 7.43ꢀ7.47 (m, 1 H), 7.58ꢀ7.62 (m, 1 H); 13C NMR (62.9 MHz, CDCl3): δ=
21.1, 103.2, 110.5, 120.1, 121.1, 122.2, 124.3, 128.1, 129.2, 130.1, 136.3, 137.3; Anal. Calcd
for C15H13N: C, 86.92; H, 6.32; N, 6.76%. Found: C, 86.57; H, 6.55; N, 6.88%.
1-Pyridin-2-yl-1H-indole (3j)
Dark brown oil, 1H NMR (250 MHz, CDCl3): δ= 6.56 (d, J= 3.5 Hz, 1 H), 6.97 (t, J= 6.0
Hz, 1 H), 7.00ꢀ7.25 (m, 3 H), 7.49ꢀ7.56 (m, 3 H), 8.09 (d, J= 8.2 Hz, 1 H), 8.36ꢀ8.39 (m, 1
H); 13C NMR (62.9 MHz, CDCl3): δ= 105.7, 113.3, 114.6, 120.2, 121.2, 121.5, 123.3, 126.1,
130.6, 135.2, 138.5, 149.0, 152.5; Anal. Calcd for C13H10N2: C, 80.39; H, 5.19; N, 14.42%.
Found: C, 80.57; H, 5.09; N, 14.34%.
2-Methyl-1-phenyl-1H-indole (3k)
Dark brown oil, 1H NMR (250 MHz, CDCl3): δ= 2.22 (s, 3 H), 6.32 (s, 1 H), 7.00ꢀ7.07 (m, 3
H), 7.25ꢀ7.29 (m, 2 H), 7.36ꢀ7.51 (m, 4 H); 13C NMR (62.9 MHz, CDCl3): δ= 13.4, 101.3,
110.0, 119.6, 120.0, 121.0, 127.7, 128.0, 128.2, 129.4, 137.0, 138.2; Anal. Calcd for
C15H13N: C, 86.92; H, 6.32; N, 6.76%. Found: C, 86.72; H, 6.45; N, 6.83%.
1-Phenyl-1H-benzimidazole (3l)
Brown oil, 1H NMR (250 MHz, CDCl3): δ= 7.32ꢀ7.36 (m, 2 H), 7.44ꢀ7.61 (m, 6 H),
14

Page 15 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
7.89ꢀ7.90 (m, 1 H), 8.17 (s, 1 H); 13C NMR (62.9 MHz, CDCl3): δ= 110.5, 120.6, 122.8,
123.7, 124.0, 128.0, 130.0, 136.3, 142.8, 144.2; Anal. Calcd for C13H10N2: C, 80.39; H, 5.19;
N, 14.42%. Found: C, 80.51; H, 5.01; N, 14.48%.
1-Pyridin-2-yl-1H-benzimidazole (3n)
Brown oil, 1H NMR (250 MHz, CDCl3): δ= 7.26ꢀ7.39 (m, 3 H), 7.58 (d, J= 8.2 Hz, 1 H),
7.86ꢀ7.93 (m, 2 H), 8.06 (d, J= 7.8 Hz, 1 H), 8.58ꢀ8.62 (m, 2 H); 13C NMR (62.9 MHz,
CDCl3): δ= 112.6, 114.3, 120.6, 121.8, 123.3, 124.2, 132.1, 138.9, 141.3, 144.7, 149.5, 149.9;
Anal. Calcd for C12H9N3: C, 73.83; H, 4.65; N, 21.52%. Found: C, 73.62; H, 4.76; N,
21.62%.
1-Phenyl-1H-pyrrole (3o)
Dark brown oil, 1H NMR (250 MHz, CDCl3): δ= 6.27 (t, J= 4.5 Hz, 2 H), 7.00 (t, J= 4.5 Hz,
2 H), 7.12ꢀ7.18 (m, 1 H), 7.28ꢀ7.33 (m, 4 H); 13C NMR (62.9 MHz, CDCl3): δ= 110.6, 119.4,
120.6, 125.7, 129.7, 140.9; Anal. Calcd for C10H9N: C, 83.88; H, 6.34; N, 9.78%. Found: C,
83.64; H, 6.43; N, 9.93%.
1,4-Diphenylpiperazine (3p)
Dark brown solid, mp 149ꢀ150 °C, 1H NMR (250 MHz, CDCl3): δ= 3.36 (s, 8 H), 6.88ꢀ7.02
(m, 6 H), 7.28ꢀ7.34 (m, 4 H); 13C NMR (62.9 MHz, CDCl3): δ= 49.5, 116.4, 120.1, 129.2,
151.3; Anal. Calcd for C16H18N2: C, 80.63; H, 7.61; N, 11.75%. Found: C, 80.89; H, 7.52; N,
11.59%.
1-Phenyl-4-pyridin-2-ylpiperazine (3r)
Light brown solid, mp 100ꢀ101 °C, 1H NMR (250 MHz, CDCl3): δ= 3.24 (dd, J1= 7.0 Hz, J2=
5.0 Hz, 4 H), 3.64 (t, J= 5.2 Hz, 4 H), 6.56ꢀ6.65 (m, 2 H), 6.79ꢀ6.93 (m, 3H), 7.18ꢀ7.25 (m, 2
H), 7.40ꢀ7.47 (m, 1 H), 8.14ꢀ8.16 (m, 1 H); 13C NMR (62.9 MHz, CDCl3): δ= 45.3, 49.2,
107.2, 113.6, 116.3, 120.1, 129.2, 137.6, 148.0, 151.3, 159.4; Anal. Calcd for C15H17N3: C,
75.28; H, 7.16; N, 17.56%. Found: C, 75.38; H, 7.27; N, 17.35%.
N,N-Dibutylaniline (3s)
Black oil, 1H NMR (250 MHz, CDCl3): δ= 0.88 (t, J= 7.5 Hz, 6 H), 1.20ꢀ1.32 (m, 4 H), 1.46ꢀ
1.55 (m, 4 H), 3.18 (t, J= 7.5 Hz, 4 H), 6.54ꢀ6.58 (m, 3 H), 7.09ꢀ7.17 (m, 2 H); 13C NMR
(62.9 MHz, CDCl3): δ= 14.0, 20.4, 29.4, 50.8, 111.6, 115.0, 129.2, 148.2;
N,N-Diethylaniline (3t)
Dark brown oil, 1H NMR (250 MHz, CDCl3): δ= 1.18 (t, 6 H), 3.37 (q, 4 H), 6.63ꢀ6.73 (m, 3
H), 7.20ꢀ7.27 (m, 2 H); 13C NMR (62.9 MHz, CDCl3): δ= 12.6, 44.3, 111.8, 115.3, 129.3,
147.8; Anal. Calcd for C10H15N: C, 80.48; H, 10.13; N, 9.39%. Found: C, 80.25; H, 10.03; N,
9.72%.
1,4-Diphenyl-1H-1,2,3-triazole (7a): White solid; mp: 174ꢀ175 oC (175ꢀ177 oC)58; 1H NMR
(250 MHz, CDCl3) δ: 7.26 (d, J= 1.6 Hz, 1H), 7.38 (t, J= 7.6 Hz, 1H), 7.47 (t, J=7.6 Hz, 2H),
7.56 (t, J= 8.0 Hz, 2H), 7.81 (d, J= 8.0 Hz, 2H), 7.93 (d, J= 7.6 Hz, 2H), 8.20 (s, 1H); 13C
NMR (62.9 MHz, CDCl3) δ: 117.6, 120.6, 125.9, 128.4, 128.8, 128.9, 129.8, 130.3, 137.1,
148.5; IR (KBr, Cmꢀ1): 3118, 2919, 2356, 1729, 1463, 1236, 1070.
1-(4-Hydroxyphenyl)-4-phenyl-1H-1,2,3-triazole (7b): White solid; mp: 207ꢀ208 oC (206ꢀ
208 oC)58; 1H NMR (250 MHz, CD3OD) δ: 6.96 (d, J= 9.2 Hz, 2H), 7.37 (t, J= 6.0 Hz, 1H),
15

RSC Advances
Page 16 of 21
View Article Online
DOI: 10.1039/C6RA16646F
7.46 (t, J= 7.6 Hz, 2H), 7.68 (d, J= 6.4 Hz, 2H), 7.91 (d, J= 7.2 Hz, 2H), 8.75 (s, 1H); 13C
NMR (62.9 MHz, DMSOꢀd6) δ: 116.0, 119.5, 121.9, 125.3, 128.1, 128.8, 128.9, 130.4, 146.9,
157.8; IR (KBr, Cmꢀ1): 3135, 1603, 1520, 1229, 1055.
1-(4-Methoxyphenyl)-4-phenyl-1H-1,2,3-triazole (7c): White solid; mp: 156ꢀ157 oC (155ꢀ
159 oC)58; 1H NMR (250 MHz, CDCl3) δ: 3.89, (s, 3H), 7.06 (d, J= 7.2 Hz, 2H), 7.35 (t, J=
7.2 Hz, 1H), 7.46 (t, J= 7.4 Hz, 2H), 7.71 (d, J= 7.4 Hz, 2H), 7.92 (d, J= 7.2 2H), 8.11 (s,
1H); IR (KBr, Cmꢀ1): 3133, 2956, 2356, 1722, 1517, 1229, 1041.
1-(4-Phenoxy-phenyl)-4-phenyl-1H-1,2,3-triazole (7d): White solid; mp: 170ꢀ171 oC (171ꢀ
173 oC)58; 1H NMR (250 MHz, CDCl3) δ: 7.08 (d, J= 8.5 Hz, 2H), 7.16 (m, 3H), 7.34 (m,
3H), 7.44 (t, J= 7.7 Hz, 2H), 7.74 (d, J= 8.9 Hz, 2H), 7.92 (d, J= 8.3 Hz, 2H), 8.15 (s, 1H);
13C NMR (62.9 MHz, CDCl3) δ: 117.8, 119.3, 119.5, 122.3, 124.2, 125.9, 128.4, 128.9,
130.0, 132.3, 148.4, 156.4, 158.0; IR (KBr, Cmꢀ1): 3125, 2923, 2356, 1585, 1511, 1247.
1-(3-Formylphenyl)-4-phenyl-1H-1,2,3-triazole (7e): White solid; mp: 164ꢀ166 oC (162ꢀ
165 oC)58; 1H NMR (250 MHz, CDCl3) δ: 7.41 (t, J= 4.0 Hz, 1H), 7.50 (t, J= 5.6 Hz, 2H),
7.77 (t, J= 8.0 Hz, 1H), 7.94 (d, J= 7.2 Hz, 2H), 7.99 (d, J= 7.6 Hz, 1H), 8.19 (d, J= 7.2 Hz,
1H), 8.30 (d, J= 7.61 Hz, 2H), 10.13 (s, 1H); 13C NMR (62.9 MHz, CDCl3) δ: 117.4, 120.1,
125.9, 128.7, 129.0, 129.9, 130.6, 130.8, 137.7, 137.8, 148.9, 190.8; IR (KBr, Cmꢀ1): 3137,
2817, 1703, 1597, 1238, 1011.
1-Thiophen-3-yl-4-phenyl-1H-1,2,3-triazole (7f): White solid; mp: 166ꢀ167 oC (164ꢀ166
oC)58; 1H NMR (250 MHz, CDCl3) δ: 7.32ꢀ7.38 (m, 1H), 7.44 (m, 1H), 7.48ꢀ7.50 (m,1H),
7.52ꢀ7.53 (m,1H), 7.61ꢀ7.62 (q, J= 1.2, 3.2 Hz,1H), 7.68 (m, 1H), 7.90 (s, 1H), 7.92 (d, J=
1.6 Hz, 1H), 8.11 (s, 1H); 13C NMR (62.9 MHz, CDCl3) δ: 114.1, 118.0, 120.9, 125.9, 127.3,
128.5, 128.9, 130.2, 135.9, 148.0; IR (KBr, Cmꢀ1): 3107, 1559, 1445, 1229, 1072.
1-(4-Hydroxyphenyl)-4-cyclohexyl-1H-1,2,3-triazole (7g): White solid; mp: 169ꢀ170 oC
(167ꢀ169 oC)58; 1H NMR (250 MHz, CDCl3) δ: 1.23ꢀ1.35 (m, 2H), 1.38ꢀ1.50 (m, 3H), 1.76
(m, 1H), 1.85 (m, 2H), 2.14 (m, 2H), 2.86 (m, 1H), 6.25 (brs, OH), 7.03 (d, J= 8.8 Hz, 2H),
7.56ꢀ7.60 (m, 3H); 13C NMR (62.9 MHz, CDCl3) δ: 26.0, 26.1, 33.0, 35.2, 116.6, 118.1,
122.2, 130.0, 154.0, 157.4; IR (KBr, Cmꢀ1): 3141, 2928, 2358, 1601, 1517, 1225, 1063.
1-(4-Methoxyphenyl)-4-cyclohexyl-1H-1,2,3-triazole (7h): White solid; mp: 91ꢀ92 oC (90ꢀ
93 oC)58; 1H NMR (250 MHz, CDCl3) δ: 1.26ꢀ1.30 (m, 1H), 1.40 (m, 4H), 1.80ꢀ1.90 (m, 3H),
2.18 (m, 2H), 2.82 (m, 1H), 3.82 (s, 3H), 6.98 (d, J= 6.8 Hz, 2H), 7.62 (m, 3H); 13C NMR
(62.9 MHz, CDCl3) δ: 26.2, 29.4, 33.1, 35.8, 55.0, 114.7, 117.2, 121.8, 132.5, 154.2, 159.6;
IR (KBr, Cmꢀ1): 3130, 2924, 2361, 1725, 1519, 1254, 1046.
1-(Naphth-2-yl)-4-cyclohexyl-1H-1,2,3-triazole (7i): White solid; mp: 141ꢀ142 oC (139ꢀ141
oC)58; 1H NMR (250 MHz, CDCl3) δ: 1.22ꢀ1.36 (m, 1H), 1.39ꢀ1.55 (m, 4H), 1.79 (m, 1H),
1.88 (m, 2H), 2.16 (m, 2H), 2.90ꢀ2.92 (m, 1H), 7.51ꢀ7.58 (m, 2H), 7.81 (s, 1H), 7.87ꢀ7.92 (m,
3H), 8.00 (d, J= 8.8 Hz, 1H), 8.15 (s, 1H); 13C NMR (62.9 MHz, CDCl3) δ: 26.1, 26.2, 29.7,
33.0, 35.4, 117.7, 118.1, 119.0, 126.8, 127.3, 127.9, 128.2, 129.9, 132.7, 133.3, 134.8, 154.5;
IR (KBr, Cmꢀ1): 3128, 2926, 1566, 1501, 1239, 1038.
1-(Indol-5-yl)-4-cyclohexyl-1H-1,2,3-triazole (7j): Light pink solid; mp: 138ꢀ139 oC (136ꢀ
139 oC)58; 1H NMR (250 MHz, CDCl3) δ: 1.21ꢀ1.37 (m, 2H), 1.36ꢀ1.51 (m, 3H), 1.77 (m,
16

Page 17 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
1H), 1.86 (m, 2H), 2.16 (m, 2H), 2.87 (m, 1H), 6.63 (t, J= 2.4 Hz, 1H), 7.33 (t, J= 2.8 Hz,
1H), 7.47ꢀ7.56 (m, 2H), 7.68 (s, 1H), 7.91 (d, J= 1.6 Hz, 1H), 8.48 (s, 1H); 13C NMR (62.9
MHz, CDCl3) δ: 26.1, 26.2, 33.1, 35.4, 103.3, 111.8, 113.2, 115.9, 118.5, 126.2, 128.0, 130.9,
135.4, 154.0; IR (KBr, Cmꢀ1): 3349, 2921, 2360, 1444, 1223, 1046.
1-(4-Hydroxyphenyl)-4-octyl-1H-1,2,3-triazole (7k): Light pink solid; mp: 99ꢀ101 oC (98ꢀ
100 oC)58; 1H NMR (250 MHz, CDCl3) δ: 0.88 (t, J= 6.8 Hz, 3H), 1.26ꢀ1.39 (m, 10H), 1.72ꢀ
1.76 (m, 2H), 2.79 (t, J= 7.6 Hz, 2H), 7.06 (d, J= 7.2 Hz, 2H), 7.58 (d, J= 6.8 Hz, 2H), 7.64
(s, 1H); 14.1, 22.7, 25.5, 29.2 (2 C), 29.3, 29.4, 31.9, 116.7, 119.5, 122.3, 129.9, 148.8,
157.8; IR (KBr, Cmꢀ1): 3122, 2920, 1600, 1236, 1057.
1-(4-Methoxyphenyl)-4-octyl-1H-1,2,3-triazole (7l): Light yellow solid; mp: 54ꢀ56 oC (53ꢀ
55 oC)58; 1H NMR (250 MHz, CDCl3) δ: 0.94 (t, J= 6.4 Hz, 3H), 1.27ꢀ1.43 (m, 10H), 1.72
(m, 2H), 2.82 (t, J= 7.6 Hz, 2H), 3.89 (s, 3H), 7.03 (d, J= 6.8 Hz, 2H), 7.61ꢀ7.71 (m, 3H); 13C
NMR (62.9 MHz, CDCl3) δ: 14.1, 22.7, 25.7, 29.4, 29.5, 29.7, 30.4, 31.9, 55.6, 114.7, 119.0,
122.4, 132.5, 149.0, 159; IR (KBr, Cmꢀ1): 3127, 2919, 2357, 1725, 1521, 1256, 1048.
Acknowledgements
This work was supported by council of Iran National Science Foundation and University of
Shiraz from the Iran Society for the Promotion of Science.
References
1 S. U. Son, Y. J. Jang, J. Park, H. B. Na, H. M. Park, H. J. Yun, J. Lee and T. Hyeon, J. Am. Chem.
Soc, 2004, 126, 5026.
2 H. M. Chen, C. K. Chen, R. S. Liu, L. Zhang, J. J. Zhang and D. P. Wilkinson, Chem. Soc. Rev,
2012, 41, 5654.
3 Z. J. Han, F. Qiu, R. Eisenberg, P. L. Holland and T. D. Krauss, Science, 2012, 338, 1321.
4 M. Esmaeilpour, A. R. Sardarian and J. Javidi, Catal. Sci. Technol, 2016, 6, 4005.
5 P. D. Stevens, G. Li, J. Fan, M. Yen and Y. Gao, Chem. Commun, 2005, 4435.
6 Y. Zhu, L. P. Stubbs, F. Ho, R. Liu, C. P. Ship, J. A. Maguire and N. S. Hosmane, Chem. Cat.
Chem, 2010, 2, 365.
7 M. Esmaeilpour, J. Javidi, F. Dehghani and F. Nowroozi Dodeji, New J. Chem, 2014, 38, 5453.
8 S. Ko and J. Jang, Angew. Chem, 2006, 118, 7726 .
9 P. Li, L. Wang, L. Zhang and G. W. Wang. Adv. Synth. Catal, 2012, 354, 1307.
10 M. Esmaeilpour, J. Javidi and Maryam Zandi, Mater. Res. Bull, 2014, 55, 78.
11 M. Cai, J. Peng, W. Hao and G. Ding, Green Chem, 2011, 13, 190.
12 Y. M. A. Yamada, K. Takeda, H. Takahashi and S. Ikegami, J. Org. Chem, 2003, 68, 7733.
17

RSC Advances
Page 18 of 21
View Article Online
DOI: 10.1039/C6RA16646F
13 J. Liu, X. Huo, T. Li, Z. Yang, P. Xi, Z. Wang and B. Wang. Chem. Eur. J, 2014, 20, 11549.
14 N. Audic, H. Clavier, M. Mauduit and J. C. Guillemin, J. Am. Chem. Soc, 2003, 125, 9248.
15 A. Schatz, M. Hager and O. Reiser, Adv. Funct. Mater, 2009, 19, 2109.
16 M. Esmaeilpour, J. Javidi, F. Dehghani and F. Nowroozi Dodeji, RSC Adv, 2015, 5, 26625.
17 D. Zhang, C. Zhou, Z. Sun, L. Z. Wu, C. H. Tung and T. Zhang, Nanoscale, 2012, 4, 6244.
18 M. B. Gawande, P. S. Brancoa and R. S. Varma, Chem. Soc. Rev, 2013, 42, 3371.
19 M. Esmaeilpour, J. Javidi and M. Zandi, New J. Chem, 2015, 39, 3388.
20 M. M. J. Modo and J. W. M. Bulte, Molecular and cellular MR imaging. CRC Press, Boca Raton,
2007.
21 S. Boutry, S. Laurent, L. V. Elst and R. N. Muller, Contrast Med. Mol. Imaging, 2006, 1, 15.
22 J. Javidi and M. Esmaeilpour, Colloid. Surfaces B, 2013, 102, 265.
23 M. M. Miller, G. A. Prinz, S. F. Cheng and S. Bounnak, Appl. Phys. Lett, 2002, 81, 2211.
24 H. Pardoe, P. R. Clark, T. G. St Pierre, P. Moroz and S. K. A. Jones, Magn. Reson. Imag, 2003,
21, 483.
25 M. Esmaeilpour, A. R. Sardarian, A. Jarrahpour, E. Ebrahimi and J. Javidi, RSC Adv, 2016, 6,
43376.
26 A.K. Gupta and M. Gupta, Biomaterials, 2005, 26, 3995.
27 J. Javidi, M. Esmaeilpour and M. Rajabnia Khansari, RSC Adv, 2015, 5, 73268.
28 M. Esmaeilpour, J. Javidi, F. Nowroozi Dodeji and M. Mokhtari Abarghoui, Transition. Met.
Chem, 2014, 39, 797.
29 M. Esmaeilpour and J. Javidi. J. Chin. Chem. Soc, 2015, 62, 614.
30 D. Kim, N. Lee, M. Park, B. Y. Kim, K. An and T. Hyeon, J. Am. Chem. Soc, 2009, 131, 454.
31 R. Xiong, Y. Wang, X. Zhang, C. Lu and L. Lan, RSC Adv, 2014, 4, 6454.
32 Z. Markova, K. Siskova, J. Filip, K. Safarova, R. Prucek, A. Panacek, M. Kolar and R. Zboril,
Green. Chem, 2012, 14, 2550.
33 M. L. Quan, P. Y. S. Lam, Q. Han, D. J. P. Pinto, M. Y. He, R. Li, C. D. Ellis, C. G. Clark, C. A.
Teleha, J. H. Sun, R. S. Alexander, S. Bai, J. M. Luettgen, R. M. Knabb, P. C. Wong and P. R.
Wexler, J. Med. Chem, 2005, 48, 1729.
34 H. Zhang, Q. Cai, and D. Ma, J. Org. Chem, 2005, 70, 5164.
35 F. Ullmann, Ber. Dtsch. Chem. Ges, 1903, 36, 2382.
18

Page 19 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
36 J. Hassan, M. Sevignon, C. Gozzi, E. Schulz and M. Lemaire, Chem. Rev, 2002, 102, 1359.
37 H. J. Cristau, P. P. Cellier, J. F. Spindler and M. Taillefer, Chem. Eur. J, 2004, 10, 5607.
38 A. Klapars, X. Huang and S. L. Buchwald, J. Am. Chem. Soc, 2002, 124, 7421.
39 H. J. Cristau, P. P. Cellier, J. F. Spindler and M. Taillefer, Eur. J. Org. Chem, 2004, 695.
40 D. M. T. Chan, K. L. Monaco, R. Li, D. Bonne, C. G. Clark and P. Y. S. Lam, Tetrahedron Lett,
2003, 44, 3863.
41 D. Schweinfurth, S. Strobel and B. Sarkar, Inorg. Chim. Acta, 2011, 374, 253.
42 D. Amantini, F. Fringuelli, O. Piermatti, F. Pizzo, E. Zunino and L. Vaccaro, J. Org. Chem, 2005,
70, 6526.
43 Y. Xia, Z. Fan, J. Yao, Q. Liao, W. Li, F. Qu and L. Peng, Bioorg. Med. Chem. Lett, 2006, 16,
2693.
44 V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless, Angew. Chem. Int. Ed, 2002, 41,
2596.
45 E. Frank, J. Molnár, I. Zupkó, Z. Kádár and J. Wölfling, Steroids, 2011, 76, 1141ꢀ1148.
46 S. Chassaing, A. S. S. Sido, A. Alix, M. Kumarraja, P. Pale and J. Sommer, Chem. Eur. J, 2008,
14, 6713.
47 B. H. Lipshutz and B. R. Taft, Angew. Chem. Int. Ed, 2006, 45, 8235.
48 T. Miao and L. Wang, Synthesis, 2008, 363.
49 C. Girard, E. Önen, M. Aufort, S. Beauvière, E. Samson and J. Herscovici, Org. Lett, 2006, 8,
1689.
50 M. Meldal and C. W. Tomøe, Chem. Rev, 2008, 108, 2952.
51 J. Y. Kim, J. C. Park, H. Kang, H. Song and K. H. Park, Chem. Commun, 2010, 46, 439.
52 F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless and V. Fokin, J.
Am. Chem. Soc, 2005, 127, 210.
53 J. Jlalia, F. Gallier, N. BrodieꢀLinder, J. Uziel, J. Augé and N. LubinꢀGermain, J. Mol. Catal. A
Chem, 2014, 393, 56.
54 Y. Masuyama, K. Yoshikawa, N. Suzuki, K. Hara and A. Fukuoka, Tetrahedron Lett, 2011, 52,
6916.
55 K. Namitharan, M. Kumarraja and K. Pitchumani, Chem. Eur. J, 2009, 15, 2755.
56 M. Esmaeilpour and J. Javidi, J. Chin. Chem. Soc, 2015, 62, 328.
57 M. Esmaeilpour, J. Javidi and S. Zahmatkesh, Appl. Organomet. Chem, 2016, DOI 10.1002/aoc.
3518.
19

RSC Advances
Page 20 of 21
View Article Online
DOI: 10.1039/C6RA16646F
58 S. Mohammed, A. K. Padala, B. A. Dar, B. Singh, B. Sreedhar, R. A. Vishwakarma and S. B.
Bharate, Tetrahedron, 2012, 68, 8156.
59 R. H. Crabtree, Chem. Rev, 2012, 112, 1536.
60 A. Biffis, M. Zecca and M. Basato, Eur. J. Inorg. Chem, 2001, 1131.
61 J. Javidi and M. Esmaeilpour, Mater. Res. Bull, 2016, 73, 409.
62 M. Esmaeilpour, J. Javidi, F. Nowroozi Dodeji and H. Hassannezhad, J. Iran. Chem. Soc, 2014,
11, 1703.
20

Page 21 of 21
RSC Advances
View Article Online
DOI: 10.1039/C6RA16646F
Graphical abstract
N(H)-heterocycle
R
or
Ar-X
NaN3
DM
F
R2NH
Ar
B(OH)2
N
N
Ar-N-heterocycle
Ar
N
or
Ar-NR2
R
:Fe3O4@SiO2-DAQ-Cu(II)